An anti-ubiquitin antibody response in transitional cell carcinoma of the urinary bladder

PloS One
Peter U ArdeltBurkhard Kneitz

Abstract

To use combinatorial epitope mapping ("fingerprinting") of the antibody response to identify targets of the humoral immune response in patients with transitional cell carcinoma (TCC) of the bladder. A combinatorial random peptide library was screened on the circulating pool of immunoglobulins purified from an index patient with a high risk TCC (pTa high grade plus carcinoma in situ) to identify corresponding target antigens. A patient cohort was investigated for antibody titers against ubiquitin. We selected, isolated, and validated an immunogenic peptide motif from ubiquitin as a dominant epitope of the humoral response. Patients with TCC had significantly higher antibody titers against ubiquitin than healthy donors (p<0.007), prostate cancer patients (p<0.0007), and all patients without TCC taken together (p<0.0001). Titers from superficial tumors were not significantly different from muscle invasive tumors (p = 0.0929). For antibody response against ubiquitin, sensitivity for detection of TCC was 0.44, specificity 0.96, positive predictive value 0.96 and negative predictive value 0.41. No significant titer changes were observed during the standard BCG induction immunotherapy. This is the first report to demonstrate an anti-u...Continue Reading

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Methods Mentioned

BETA
phage display
Assay
electrophoresis
enzyme-linked immunosorbent assay
ELISA
ELISAs

Software Mentioned

Clustal W

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